The goal of the proposed program is to discover, and begin development of, novel compounds with potential as therapeutic agents against hepatitis C virus (HCV) and human rhinovirus. HCV is one of the agents of viral hepatitis causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Human rhinovirus is the primary causative agent of the common cold and can exacerbate other disease states. There are no adequate treatments available for HCV or human rhinovirus. With SBIR Phase I funding, in vitro HCV and rhinovirus drug discovery systems were established, several HCV and rhinovirus inhibitors identified, and two of these found to inhibit viral replication in cell culture. With SBIR Phase II funding, the large-scale screening programs will be expanded and resulting inhibitors tested in surrogate HCV infection and rhinovirus infection assays in cell culture and in novel animal models. Lead compounds will be generated by chemical modification.of samples with the most significant activities. If promising lead compounds are discovered in Phase II, they will be further developed through preclinical and clinical trials during Phase III. PROPOSED COMMERCIAL APPLICATION: This research will result in the identification of novel anti-HCV and anti-rhinovirus drugs.